The compound represented by the following formula is known as one example of water-soluble prodrugs (for instance, refer to Patent Document 1 and Patent Document 2). This compound is a water-soluble azole prodrug useful for in the treatment of serious systemic fungal infection.

In addition, this water-soluble prodrug is also known to be preparable by the following scheme (refer to Patent Document 2 below).

In the above formula, t-Bu represents tert-butyl, THF represents tetrahydrofuran and TFA represents trifluoroacetic acid. As illustrated in the above scheme, in order to prepare the water-soluble azole prodrugs, first, chloromethylphosphates (corresponding to Y in the above scheme) and active drug compounds (corresponding to X in the above scheme) having a hydroxyl group are reacted to obtain an intermediate compound Z, then, the intermediate compound Z is subjected to deprotection reaction to be converted into the water-soluble azole prodrugs. Introducing in this way a phosphonooxymethyl moiety into a hydroxyl group-containing drug is known as a process for preparing the water-soluble prodrugs of the hydroxyl group-containing drug. Note that the term “prodrug” means a derivative of a drug compound, which reverts in vivo to the original drug compound (hereinafter sometimes referred to as “parent compound”); water-soluble prodrug formulation of active ingredients is often the subject of research and development.
Then, when the deprotection reaction of the above intermediate compound Z is followed by sodium salt formation, the reaction yield from these two steps has been reported to be approximately 12% (following scheme: for example, refer to Patent Document 1). Note that, in the following formula, t-Bu represents tert-butyl.

However, since the intermediate compound Z deprotection reactions disclosed in Patent Document I and Patent Document 2 use a halogen-based solvent such as methylene chloride, industrialization thereof would place a large burden on the environment, accompanied by the complexity of waste liquid treatment.
In addition, as described earlier, since the reaction yield when deprotection reaction is followed by sodium salt formation is 12%, with this reaction yield, the reaction cannot be called effective from the point of view of industrial preparation, and is extremely inadequate for large amount syntheses at an industrial scale. Therefore, additional improvements are sought regarding the deprotection reaction of the above-mentioned intermediate compound Z from the point of view of industrial preparation.
Meanwhile, as a preferred mode of water-soluble azole prodrug, a pharmacologically acceptable salt of the prodrug is disclosed in the above Patent Document 1. In addition, in Patent Document 1, water-solubility is reported to be better than that of the parent compound, by turning the prodrug into a salt. Specifically, a dilysine salt and a tert-butyl amine salt of water-soluble azole prodrugs are disclosed in Patent Document 1; however, improvement of physical properties of the salt per se is sought, in addition to solubility in water.    [Patent Document 1] Published Japanese Translation of a PCT Application No. 2003-520235 (International Publication No. WO01/52852)    [Patent Document 2] Published Japanese Translation of a PCT Application No. 2004-518640 (International Publication No. WO02/42283)